PII-005 - THERAPEUTIC DRUG MONITORING CAN GUIDE THE INTRAVENOUS-TO-SUBCUTANEOUS SWITCH OF INFLIXIMAB AND VEDOLIZUMAB: A PHARMACOKINETIC SIMULATION STUDY.

Z. Wang¹, B. Verstockt^2,1, J. Sabino^2,1, M. Ferrante^2,1, S. Vermeire^2,1, E. Dreesen^1,3; ¹Katholieke Universiteit Leuven, Leuven, Belgium, ²University Hospitals Leuven, Leuven, Belgium, ³University of California, San Francisco, San Francisco, CA, USA.

Background: Subcutaneous (SC) formulations of infliximab (IFX) and vedolizumab (VDZ) were recently approved for maintenance treatment of patients with inflammatory bowel disease. However, further investigation is required to identify the patients most likely to benefit from intravenous (IV)-to-SC switch. We hypothesize that therapeutic drug monitoring (TDM) can guide the IV-to-SC switch.

Methods: Population pharmacokinetic (popPK) simulations were performed with previously published popPK models to explore the exposure profiles following various label and off-label IV-to-SC dosing scenarios (NONMEM 7.5).(1-3) All virtual patients received IV IFX or VDZ at treatment weeks 0, 2, 6, 14, 22, and 30, and then switched to every two weeks (Q2W) or Q1W SC dosing.

Results: Following IV-to-SC switch according to label, the serum trough concentrations (Ctrough) will gradually increase over eight weeks (for IFX) and 16 weeks (for VDZ) before reaching the new steady state (SS). A linear relationship was observed between IV and SC Ctrough,ss for both drugs, allowing the prediction of SC Ctrough,ss based on previous IV Ctrough,ss. Administering the first SC dose four instead of eight weeks after the last IV dose will hit SS much faster (immediately for IFX and in two months for VDZ), thereby allowing earlier TDM and avoiding the risk of temporary underexposure. Depending on the belief whether it is Ctrough,ss or area under drug concentration-time curve that drives therapeutic response, patients who were on escalated IV dosing regimens may need Q1W SC to guarantee similar exposure before versus after switch.

Conclusion: We performed popPK simulations to inform clinicians how to integrate TDM of IFX and VDZ into their clinical practice as a tool to monitor patients and guide decision-making on the optimal dosing strategy.

(1) Assessment Report on extension(s) of marketing authorisation: Remsima. EMA/CHMP/548703/2019. European Medicines Agency. Published online Sep 19, 2019. Accessed Sep 14, 2022. https://www.ema.europa.eu/en/documents/assessment-report/remsima-epar-public-assessment-report_en.pdf.
(2) Rosario, M., et al. Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease. Aliment Pharmacol Ther. 42, 188-202 (2015).
(3) Rosario, M., Polhamus, D., Chen C., Sun, W. & Dirks, N.L. A vedolizumab population pharmacokinetic model including intravenous and subcutaneous formulations for patients with ulcerative colitis. J Crohns Colitis. 13, S357 (2019).